Back to Search
Start Over
Antineoplastic potency of arylchloroethylurea derivatives in murine colon carcinoma.
- Source :
-
Investigational new drugs [Invest New Drugs] 2004 Nov; Vol. 22 (4), pp. 369-78. - Publication Year :
- 2004
-
Abstract
- In a search for new antineoplastic agents the lead compound N-(4-tert-butylphenyl)-N'-(2-chloroethyl)urea (CEU-22) of a series of 1-aryl-3-(2-chloroethyl)ureas and its iodinated bioisostere CEU-98, were previously selected on the basis of their cytotoxicity and the potent tropism for the intestinal tract (evidenced for CEU-22). In this study, we investigated the antitumour profile of these two drugs for the indication of colon cancer. In vitro, we found that micromolar concentrations of both CEU-22 and CEU-98 inhibited proliferation of DLD-1, Caco-2, HT-29, SW-948 and CT-26 lines. In vivo, a high inhibition of tumour growth and a life span increase were observed when BALB/c mice grafted subcutaneously with CT-26 cells received 5 daily intratumoural injections of each drug. When administered by the intraperitoneal route according to an intermittent schedule starting Day 1 or Day 7 post-implant, only CEU-98 demonstrated antitumour activity ( T / C = 29% for the Day-1,5,9-treatment versus 40% for the Day-7,11,15-treatment) and a life span increase around 40% for the two protocols. These results make CEU-98 a candidate for further investigations with a view to developing an efficacious treatment of colorectal cancer.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Cell Line, Tumor
Drug Administration Schedule
Drug Screening Assays, Antitumor
Humans
Injections, Intraperitoneal
Male
Maximum Tolerated Dose
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Phenylurea Compounds administration & dosage
Antineoplastic Agents pharmacology
Colorectal Neoplasms drug therapy
Phenylurea Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0167-6997
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Investigational new drugs
- Publication Type :
- Academic Journal
- Accession number :
- 15292707
- Full Text :
- https://doi.org/10.1023/B:DRUG.0000036679.12112.4c